Asthma is a common chronic pulmonary disorder, associated with mucus hyperproduction, persistent pulmonary inflammation, airway hyperresponsiveness, and tissue remodeling (1, 2). Similarly, other lung related disease states such as cystic fibrosis and chronic obstructive pulmonary disease are characterized by one or more of these symptoms, which contribute to patient morbidity and mortality, and for which current therapies are not always sufficient for successful treatment.
While there are many mucolytics and agents targeting airway fluid production, there is a lack of therapeutic agents that directly target transcriptional networks critical for differentiation of mucin-producing goblet cells. Traditionally, transcription factors have been considered “undrugable” targets, such that active agents directed to the modulation of transcription factors to treat disease have not been considered feasible and have not been actively pursued.
The instant disclosure addresses one or more of the aforementioned problems in the art.